Canadian Journal of Cardiology 30 (2014) 96e101

Clinical Research

The Effect of Intravenous Vitamin C Infusion on

Periprocedural Myocardial Injury for Patients Undergoing
Elective Percutaneous Coronary Intervention
Zhi Jian Wang, MD, Wen Kun Hu, MD, Yu Yang Liu, MD, Dong Mei Shi, MD,
Wan Jun Cheng, MD, Yong He Guo, MD, Qing Yang, MD, Ying Xin Zhao, MD, and
Yu Jie Zhou, MD, PhD
Department of Cardiology, Anzhen Hospital, Capital Medical University, Beijing, China

See editorial by Gebhard and Tardif, pages 3-5 of this issue.

ABSTRACT



RESUM
E

Background: This small study has determined the effect of vitamin C

on myocardial reperfusion in patients undergoing elective percutaneous coronary intervention (PCI). This study was to explore whether
antioxidant vitamin C infusion before the procedure is able to affect
the incidence of periprocedural myocardial injury (PMI) in patients
undergoing PCI.
Methods: In this prospective single-centre randomized study, 532
patients were randomized into 2 groups: the vitamin C group, which
received a 3-g vitamin C infusion within 6 hours before PCI, and
a control group, which received normal saline. The primary end point
was the troponin Iedened PMI, and the second end point was the
creatine kinase (CK)-MBedened PMI. Separate analyses using both
end points were performed. PMI was dened as an elevation of cardiac
biomarker values (CK-MB or troponin I) > 5 times the upper limit of
normal (ULN), alone or associated with chest pain or ST-segment or Twave changes.

tude petite e
chelle a de
termine
 leffet de la
Introduction : Cette e
vitamine C lors de reperfusion myocardique chez les patients subissant
e (ICP) e
lective. Cette e
tude
une intervention coronarienne percutane
avait pour but dexaminer si la perfusion de vitamine C (antioxydant)
sion
avant une intervention est capable de modier lincidence dune le
riope
ratoire (PMI : periprocedural myocardial injury)
myocardique pe
chez les patients subissant une ICP.
thodes : Dans cette e
tude ale
atoire unicentrique prospective, 532
Me
taient re
partis au hasard en 2 groupes : le groupe de
patients e
vitamine C, qui recevait une perfusion de 3 g de vitamine C dans les 6
ce
dant lICP, et un groupe te
moin, qui recevait le solute

heures pre
tait la PMI
physiologique salin. Le critre de jugement principal e
nie par la troponine I, et le second critre de jugement e
tait la PMI
de
nie par la cre
atine-kinase (CK)-MB. Des analyses distinctes utilisant
de
taient re
alise
es. La PMI e
tait de
nie
les deux critres de jugement e
 le
vation des valeurs du biomarqueur cardiaque (CK-MB
comme une e

Periprocedural myocardial injury (PMI), which presents with

cardiac biomarker elevation, is common and occurs in up to
5% to 30% of patients after otherwise successful elective
percutaneous coronary intervention (PCI).1-3 Although the
clinical signicance of PMI has been questioned by several
analyses,4-6 multiple studies have shown that PMI is associated
with increased mortality with a graded risk related to the
extent of creatine kinase-MB (CK-MB) or cardiac troponin
elevation.7-12 In some studies, even a minor elevation of cardiac
biomarker was found to be related to a signicantly increased

risk of late mortality.10-12 Many mechanisms, such as distal

embolization, side branch occlusion, coronary dissection, and
disruption of collateral ow, may account for the occurrence of
PMI.
Increased oxidative stress has been proposed to potentially
contribute to the pathogenesis of PMI. An elevation of F2isoprostane, a stable end product of lipid peroxidation, has
been found in coronary or systemic venous blood samples
after PCI but not after diagnostic angiography.13 Vitamin C,
also known as ascorbic acid, is a water-soluble antioxidant
molecule that scavenges reactive oxygen and nitrogen species
and inhibits oxidative damage to important biological
macromolecules, including DNA, proteins, and lipids.
Recently, a prospective single-centre randomized study
involving 56 patients has shown that intravenous infusion of
vitamin C before a procedure was associated with improved
myocardial reperfusion in patients undergoing PCI.14
However, the impact of vitamin C on PMI has not been

Received for publication June 25, 2013. Accepted August 9, 2013.

Corresponding author: Dr Ying Xin Zhao, Department of Cardiology,
Anzhen Hospital, Capital Medical University, Anzhen Avenue #2, Chaoyang
District, Beijing, 100029, China. Tel.: 86-010-64556489; fax: 86-01064442234.
E-mail: zyingxinmi@163.com
See page 100 for disclosure information.

0828-282X/$ - see front matter 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.cjca.2013.08.018

Wang et al.
Effect of Vitamin C on Myocardial Injury

97

Results: After PCI, the incidence of PMI was reduced, whether dened
by troponin or by CK-MB, compared with the control group (troponin I,
10.9% vs 18.4%; P 0.016; CK-MB, 4.2% vs 8.6%; P 0.035).
Logistic multivariate analysis showed that preprocedure use of vitamin
C is an independent predictor of PMI either dened by troponin I (odds
ratio [OR], 0.56; 95% condence interval [CI], 0.33-0.97; P 0.037) or
by CK-MB (OR, 0.37; 95% CI, 0.14-0.99; P 0.048).
Conclusions: In patients undergoing elective PCI, preprocedure intravenous treatment with vitamin C is associated with less myocardial
injury.

rieure de la normale (LSN), seul

ou troponine I) > 5 fois la limite supe
 la douleur thoracique, au segment ST ou aux modicaou associe
tions de londe T.
sultats : Aprs lICP, lincidence de la PMI e
tait re
duite, soit de
nie
Re
moin
par la troponine ou par la CK-MB, comparativement au groupe te
(troponine I, 10,9 % vs 18,4 %; P 0,016; CK-MB, 4,2 % vs 8,6 %; P
e montrait que lutilisation de la
0,035). Lanalyse logistique multivarie
riode pre
ope
ratoire est un pre
dicteur inde
pendant de
vitamine C en pe
nie par la troponine I (ratio dincidence approche
 [RIA], 0,56;
la PMI de
intervalle de conance [IC] 95 %, 0,33-0,97; P 0,037) ou par la CKMB (RIA, 0,37; IC 95 %, 0,14-0,99; P 0,048).
lective, le traiteConclusions : Chez les patients subissant une ICP e
ope
ratoire entrane moins de
ment intraveineux la vitamine C en pre
sion myocardique.
le

clearly investigated in a large population. Thus, we designed

a prospective randomized controlled trial to assess whether
preprocedural infusion of vitamin C is effective for prevention
of PMI in patients undergoing elective PCI.

troponin I. Serum levels of 8-hydroxy-2-deoxyguanosine (8OHdG), a blood marker of oxidative stress, were also
measured, by enzyme-linked immunosorbent assay, in the last
30 patients (15 patients in each study arm) at baseline and 6
hours after the procedure.

Methods

PCI procedure

Patient population

All eligible patients underwent angiography rst. The

treatment strategies, including PCI, medication, or bypass
surgery, were at the discretion of the operators. All the
operators were blinded to the randomization of the study.
Only patients undergoing PCI nally were enrolled in the
present analysis. All PCI procedures followed the current
practice guidelines.16 Weight-adjusted intraprocedural
unfractionated heparin (with a goal-activated clotting time of
250-300 seconds) was administered during the procedure and
was routinely discontinued at the end of the procedure. A
loading dose of 300 to 600 mg clopidogrel was given to all
patients at least 6 hours before PCI, followed by a maintenance dose of 75 mg daily for at least 12 months unless severe
bleeding complications appeared. In addition, all patients were
administered loading doses of 300 mg aspirin the day of the
procedure and continued with 100 mg daily indenitely.

This was a prospective, single-centre, randomized placebocontrolled study. From June 2010 to December 2010,
patients scheduled for elective PCI for de novo lesions in
native coronary arteries were enrolled. Exclusion criteria
included acute ST-segment elevation or noneST-segment
elevation myocardial infarction with an elevated baseline CKMB or troponin value, cardiogenic shock, severe congenital or
valvular heart disease that required surgical treatment,
previous history of vitamin C allergy, previous coronary stent
implantation or coronary artery bypass graft, and chronic
kidney disease with an estimated glomerular ltration rate <
30 mL/min. The study design was reviewed and approved by
our institutional research ethics committee, and all patients
gave written informed consent.
Study design
All eligible patients were randomly assigned to vitamin C
treatment 2 to 6 hours before procedures (3 g of vitamin C
diluted in 250 mL of isotonic saline infused at 2.5 mL/min)
or to placebo treatment (isotonic saline infused at 2.5 mL/
min). Randomization was performed by a 1:1 ratio using
computer-generated random numbers (Fig. 1).
To access the effect of vitamin C infusion on the incidence
of PMI, blood samples were collected in the study patients
before and 6 and 24 hours after PCI to measure CK-MB and
troponin I using a radioimmunoassay analyzer. Additional
measurements were performed in case of postprocedural
symptoms suggestive of myocardial ischemia. The upper limit
of normal (ULN) was dened as the 99th percentile of the
normal population with a total imprecision of < 10%,
according to the European Society of Cardiology/American
College of Cardiology Foundation/American Heart Association/World Heart Federation universal denition.15 Normal
limits were < 6.3 ng/mL for CK-MB and < 0.04 ng/mL for

End points and denitions

The primary end point was the troponin Iedened PMI,
and the second end point was the CK-MBedened PMI.
Separate analyses using both end points were performed.
PMI was dened as an elevation of cardiac biomarker values
(CK-MB or troponin I) > 5 times ULN alone or associated
with chest pain or ST-segment or T-wave changes.
Statistical analysis
According to previous studies, we assumed a 12% incidence of primary end point events in control patients and
a 50% reduction in patients who received vitamin C treatment; a total sample size of 482 patients (241 in each group)
would provide 80% power to detect differences with an alpha
level of .05.
Data are presented as mean
standard deviation for
normally distributed continuous variables and were compared
using 2-sample independent or paired t tests as appropriate.

98

Canadian Journal of Cardiology

Volume 30 2014

Figure 1. Flow chart of patient enrollment. CABG, coronary artery bypass grafting; CK-MB, creatine kinase-MB; c-TNI, cardiac troponin I; eGFR,
estimated glomerular ltration rate; PCI, percutaneous coronary intervention.

Categorical variables are presented as frequencies and

percentages. Differences in baseline characteristics between
patients with and without depression were compared with c2
tests or exact tests if expected cell frequencies were small. The
troponin I and CK-MB data were skewed; therefore, these
values are presented as the median with the interquartile
range. The Mann-Whitney U test was used to analyze the
difference between the medians in both groups. Independent
predictors of end points were identied using binary logistic
regression. The candidate variables entered in the model
included age (continuous), sex, smoking status, history of
previous myocardial infarction, left ventricular ejection fraction, diagnosis of diabetes mellitus, hypertension, hypercholesterolemia, chronic kidney disease (estimated glomerular
ltration rate < 60 mL/min), concomitant medication,
multivessel disease, and the occurrence of major angiographic
complications. Odds ratios (ORs) and 95% condence
intervals (CIs) were calculated. All statistical analyses were 2tailed. A value of P < 0.05 was considered statistically
signicant. Analysis was performed with SPSS software,
version 16.0 for Windows (SPSS, Inc, Chicago, IL).

Results
Baseline characteristics
A total of 645 patients fullling the inclusion criteria were
initially evaluated; 31 patients were excluded because of
exclusion criteria or refusal to participate. Of 614 patients
evaluated for randomization, another 82 patients were excluded

after angiography. Finally 532 patients undergoing PCI were

enrolled in this study, 265 of whom were randomized to
vitamin C treatment and the other 267 to placebo treatment.
The baseline demographic and clinical characteristics of
patients according to randomization at the infusion treatmentdincluding age, sex, risk factor distribution, and
concomitant medication treatmentddid not differ between the
groups (Supplemental Table S1). As shown in Supplemental
Table S2, the baseline angiographic characteristics were also
very similar between the 2 groups. Angiographic success was
reached in 100% of cases in both groups. Major angiographic
complications during the procedure occurred in 11 patients
(4.2%) in the vitamin C group and 12 patients (4.5%) in the
control group (P 0.85) (Supplemental Table S3).
The effect of vitamin C on PMI
After the procedure, the incidence of PMI, dened as
elevation of troponin I values > 5 times the ULN, was
signicantly decreased by vitamin C infusion (10.9% vs
18.4%, P 0.016). The CK-MBedened PMI was also
signicantly reduced by vitamin C treatment compared with
the control group (4.2% vs 8.6%; P 0.035). Troponin I
elevation > 3 times the ULN occurred in 20.1% of the
vitamin C group and in 28.8% of the control group (P
0.020). CK-MB elevation > 3 times the ULN occurred in
6.8% of the vitamin C group and in 12.7% of the control
group (P 0.021). The proportion of patients with elevation
greater than the ULN of troponin I and CK-MB were both
lower in the vitamin C group than in the control group but
without statistical signicance (CK-MB, 17.7% vs 24.0%;

Wang et al.
Effect of Vitamin C on Myocardial Injury

99

Table 1. Baseline and post-PCI troponin I and CK-MB values

Variables
Troponin I (ng/mL)
Baseline
Median
Interquartile range
After PCI
Median
Interquartile range
CK-MB (ng/mL)
Baseline
Median
Interquartile range
After PCI
Median
Interquartile range

Vitamin C
group (n 265)

Control
group (n 267)

0.02
0.02-0.03

0.02
0.02-0.03

0.03
0.03-0.06

0.04
0.02-1.12

4.3
3.6-5.1

4.4
3.1-6.0

4.9
4.1-5.7

6.1
4.4-6.4

P value
0.214
0.017

0.104
< 0.001

CK-MB, creatine kinase-MB; PCI, percutaneous coronary intervention.

procedure was signicantly lower in the vitamin C group than

in the control group (2.4
1.0 ng/mL vs 4.1
1.1 ng/mL;
P < 0.001) (Fig. 3).

Figure 2. Percentages of patients in vitamin C group and control

group dened by a range of biomarker ratios for creatine kinase-MB
(A) and troponin I (B). ULN, upper limit of normal.

P 0.077; troponin I, 25.3% vs 32.6%; P 0.063) (Fig. 2).

Compared with the control group, prophylactic vitamin C
treatment also led to signicantly lower elevations of troponin
I and CK-MB levels after PCI (troponin I: median, 0.03 ng/
mL; interquartile range, 0.03-0.06 vs 0.04 ng/mL, interquartile range, 0.02-1.12; P 0.017; CK-MB: median 4.9
ng/mL, interquartile range, 4.1-5.7 vs 6.1 ng/mL; interquartile range, 4.4-6.4; P < 0.001) (Table 1).
The inuence of clinical, angiographic, and procedural
variables on CK-MB and troponin I elevation > 5 times the
ULN after stenting was evaluated with a multivariable binary
logistic regression analysis. Vitamin C infusion before the
procedure is an independent predictor of PMI dened by
either troponin I (OR, 0.56; 95% CI, 0.33-0.97; P 0.037)
or CK-MB (OR, 0.37; 95% CI, 0.14-0.99; P 0.048)
(Table 2).
The effect of vitamin C on oxidative stress
At baseline, there was no difference in serum values of 8OHdG between the2 groups (vitamin C group, 3.6
1.2
ng/mL vs control group, 3.8
1.2 ng/mL; P 0.580). After
the procedure, the serum level of 8-OHdG was signicantly
decreased by vitamin C infusion (P 0.011) but not by
placebo (P 0.528). The serum value of 8-OHdG after the

Discussion
This prospective randomized study showed that vitamin C
infusion before PCI was associated with a lower incidence of
PMI, dened as elevation of troponin I or CK-MB values > 5
times the ULN. The cardioprotective effect of vitamin C
may result from the inhibition of oxidative stress. PCI has
been reported to be associated with increased oxidative
stress.13,14,17-22 Most previous studies on oxidative stress have
focused on primary PCI in patients with acute ST-segment
elevation myocardial infarction,17,18 indicating that oxidative
stress associated with PCI owes more to ischemia reperfusion
injury. However, several recent studies found that elective PCI
also induced increased oxidative stress. Isoprostane F2alphaIII and isoprostane F2alpha-VI, both stable end products of
oxygen free radicalemediated lipid peroxidation, were found
to be markedly increased in coronary sinus blood samples
after elective PCI,13 suggesting that PCI induces increased
F2-isoprostane formation in the local coronary system. More
recently, plasma levels of other markers of oxidative stress,
such as ischemia-modied albumin, 8-OHdG, and 8-isoprostaglandin F2alpha, have also been reported to be elevated
after elective PCI.14,19 Although the association of oxidative
stress after PCI and cardiovascular outcomes has not been
clearly proved, a signicant positive correlation between serum
creatine phosphokinase levels and some oxidative stress
markers was found, indicating a potential correlation between
Table 2. Independent predictors of PCI-related myocardial infarction
dened by CK-MB or troponin I
Independent predictors
CK-MB > 5 ULN
Vitamin C infusion
Major angiographic complications
Troponin I > 5 ULN
Vitamin C infusion
Major angiographic complications
Diabetes

Odds ratio (95% CI)

P value

0.37 (0.14-0.99)
10.6 (10.0-28.6)

0.048
< 0.001

0.56 (0.33-0.97)
6.7 (2.8-16.3)
1.7 (1.0-2.8)

0.037
< 0.001
0.039

CK-MB, creatine kinase-MB; CI, condence interval; PCI, percutaneous

coronary intervention; ULN, upper limit of normal.

100

Canadian Journal of Cardiology

Volume 30 2014

Figure 3. Changes of serum level of 8-hydroxy-2-deoxyguanosine before and after percutaneous coronary intervention in vitamin C group (A) and
control group (B).

oxidative stress and the severity of myocardial injury (MI).20

Elevated circulating F2-isoprostanes in young healthy adults
have also been associated with markers of inammation and
endothelial dysfunction, which are both proposed to
contribute to mechanisms of PCI-related MI.21
Vitamin C, also known as ascorbic acid, is a potent watersoluble natural antioxidant that quenches reactive oxygen
species and inhibits reactive oxygen speciesemediated nitric
oxide inactivation. In addition, vitamin C can regenerate other
antioxidants, acting as a coantioxidant. Multiple studies have
shown that vitamin C is effective not only in attenuating postPCI oxidative stress but also in improving clinical
outcomes.14,17,23-28 Spargias et al found that prophylactic oral
administration of 3 g of vitamin C before a procedure and 2 g
after a procedure had a protective effect against contrastmediated nephropathy when compared with placebo in 231
patients with an elevated serum creatinine level who were
undergoing angiography or PCI.23 Preprocedure oral vitamin
C was also found to reduce the incidence of post-PCI restenosis when compared with a control group in a preliminary
study.24 A more recent randomized controlled study including
56 patients showed that a 1-g vitamin C infusion before
a procedure vs placebo was associated with a lower plasma
level of 8-OHdG and 8-iso-prostaglandin F2alpha and
improved microcirculatory reperfusion dened as thrombolysis in myocardial infarction frame count and thrombolysis in
myocardial infarction perfusion grade in patients undergoing
elective PCI.14 However, the small sample size of this study
makes it impossible to detect the effect of vitamin C on the
incidence of PMI.
Our data extended these previous ndings by demonstrating that a 3-g vitamin C infusion before PCI was associated with a lower incidence of PMI, dened as elevation of
troponin I or CK-MB values > 5 times the ULN. Although
limitation of such myocardial injury has been proved to
be benecial to the patient, the effect of vitamin C on longterm clinical outcomes should be conrmed by further
investigations.

The mechanism for the cardioprotective effect of vitamin

C has not been clearly dened. A potential role of oxidative
stress has been suggested by the fact that vitamin C infusion
blunted the increase of levels of plasma 8-OHdG, a product of
hydroxyl radical/deoxyribonucleic acid interaction. However,
a cause-effect relationship cannot be established by our study.
There are several limitations of this study. The study was
not blinded. Optimal dose, time of onset, and duration of
vitamin C use before PCI were not identied. The vitamin C
treatment protocols used in this study were arbitrary. Blood
samples for postprocedure CK-MB or troponin I measurements were drawn 6 and 24 hours after PCI. Thus, we might
have missed the opportunity to identify additional events if
more serial blood samples had been assessed. We measured
the plasma 8-OHdG level for only the last 30 patients, which
made the correlation analysis between the antioxidants and
myocardial injury unfeasible. Therefore, as we mentioned
earlier, a cause-effect relationship between a cardioprotective
effect of vitamin C and its antioxidant effect cannot be
established by our study. Furthermore, no clinical follow-up
was required after hospital discharge. Therefore, further
studies are necessary to investigate the effect of vitamin C on
the long-term clinical prognosis in this setting.
In summary, the results of this prospective randomized
study show that prophylactic infusion of vitamin Cda safe,
well-tolerated, and inexpensive antioxidantdappears to
decrease myocardial injury associated with elective PCI. The
underlying mechanisms and clinical prognosis of this cardioprotective effect need to be investigated by further studies.
Disclosures
The authors have no conicts of interest to disclose.
References
1. Califf RM, Abdelmeguid AE, Kunitz RE, et al. Myonecrosis after
revascularization procedures. J Am Coll Cardiol 1998;31:241-51.

Wang et al.
Effect of Vitamin C on Myocardial Injury

101

2. Abdelemeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG. Signicance of mild transient release of creatine kinase-MB fraction after
percutaneous coronary interventions. Circulation 1996;94:1528-36.

of Cardiology Foundation/American Heart Association Task Force on

Practice Guidelines and the Society for Cardiovascular Angiography and
Interventions. J Am Coll Cardiol 2011;58:e44-122.

3. Pervaiz MH, Sood P, Sudhir K, et al. Periprocedural myocardial infarction in a randomized trial of everolimus-eluting and Paclitaxel-eluting
coronary stents: frequency and impact on mortality according to
historic versus universal denitions. Circ Cardiovasc Interv 2012;5:
150-6.

17. Reilly MP, Delanty N, Roy L, et al. Increased formation of the isoprostanes IPF2alpha-I and 8-epi-prostaglandin F2alpha in acute coronary
angioplasty: evidence for oxidant stress during coronary reperfusion in
humans. Circulation 1997;96:3314-20.

4. Prasad A, Gersh BJ, Bertrand ME, et al. Prognostic signicance of

periprocedural versus spontaneously occurring myocardial infarction after
percutaneous coronary intervention in patients with acute coronary
syndromes: an analysis from the ACUITY (Acute Catheterization and
Urgent Intervention Triage Strategy) trial. J Am Coll Cardiol 2009;54:
477-86.
5. Fuchs S, Kornowski R, Mehran R, et al. Prognostic value of cardiac
troponin-I levels following catheter-based coronary interventions. Am J
Cardiol 2000;85:1077-82.
6. Jeremias A, Baim DS, Ho KK, et al. Differential mortality risk of postprocedural creatine kinase-MB elevation following successful versus
unsuccessful stent procedures. J Am Coll Cardiol 2004;44:1210-4.
7. Lindsey JB, Kennedy KF, Stolker JM, et al. Prognostic implications of
creatine kinase-MB elevation after percutaneous coronary intervention:
results from the Evaluation of Drug-Eluting Stents and Ischemic Events
(EVENT) registry. Circ Cardiovasc Interv 2011;4:474-80.
8. Akkerhuis KM, Alexander JH, Tardiff BE, et al. Minor myocardial
damage and prognosis: are spontaneous and percutaneous coronary
intervention-related events different? Circulation 2002;105:554-6.

18. Kaminski K, Bonda T, Wojtkowska I, et al. Oxidative stress and antioxidative defense parameters early after reperfusion therapy for acute
myocardial infarction. Acute Card Care 2008;10:121-6.
19. Pignatelli P, Tanzilli G, Carnevale R, et al. Ascorbic acid infusion blunts
CD40L upregulation in patients undergoing coronary stent. Cardiovasc
Ther 2011;29:385-94.
20. Farah R, Shurtz-Swirski R, Bolotin Y, Brezins M. Oxidative stress and
inammation due to peripheral polymorphonuclear leukocytes after
coronary angiography vs percutaneous coronary intervention. Minerva
Cardioangiol 2008;56:189-95.
21. Hozawa A, Jacobs DR Jr, Steffes MW, et al. Relationships of circulating
carotenoid concentrations with several markers of inammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk
Development in Young Adults (CARDIA)/Young Adult Longitudinal
Trends in Antioxidants (YALTA) study. Clin Chem 2007;53:447-55.
22. Sinha MK, Gaze DC, Tippins JR, Collinson PO, Kaski JC. Ischemia
modied albumin is a sensitive marker of myocardial ischemia after
percutaneous coronary intervention. Circulation 2003;107:2403-5.

9. Novack V, Pencina M, Cohen DJ, et al. Troponin criteria for myocardial

infarction after percutaneous coronary intervention. Arch Intern Med
2012;172:502-8.

23. Spargias K, Alexopoulos E, Kyrzopoulos S, et al. Ascorbic acid prevents

contrast-mediated nephropathy in patients with renal dysfunction
undergoing coronary angiography or intervention. Circulation 2004;110:
2837-42.

10. Kong TQ, Davidson CJ, Meyers SN, et al. Prognostic implication of
creatine kinase elevation following elective coronary artery interventions.
JAMA 1997;277:461-6.

24. Tomoda H, Yoshitake M, Morimoto K, Aoki N. Possible prevention of

postangioplasty restenosis by ascorbic acid. Am J Cardiol 1996;78:
1284-6.

11. Ioannidis JP, Karvouni E, Katritsis DG. Mortality risk conferred by small
elevations of creatine kinase-MB isoenzyme after percutaneous coronary
intervention. J Am Coll Cardiol 2003;42:1406-11.

25. Albabtain MA, Almasood A, Alshurafah H, Alamri H, Tamim H. Efcacy of ascorbic acid, N-acetylcysteine, or combination of both on top of
saline hydration versus saline hydration alone on prevention of contrastInduced nephropathy: a prospective randomized study. J Interv Cardiol
2013;26:90-6.

12. Prasad A, Singh M, Lerman A, et al. Isolated elevation in troponin T after

percutaneous coronary intervention is associated with higher long-term
mortality. J Am Coll Cardiol 2006;48:1765-70.
13. Iuliano L, Pratic D, Greco C, et al. Angioplasty increases coronary sinus
F2-isoprostane formation: evidence for in vivo oxidative stress during
PTCA. J Am Coll Cardiol 2001;37:76-80.
14. Basili S, Tanzilli G, Mangieri E, et al. Intravenous ascorbic acid infusion
improves myocardial perfusion grade during elective percutaneous coronary intervention: relationship with oxidative stress markers. JACC
Cardiovasc Interv 2010;3:221-9.
15. Thygesen K, Alpert JS, Jaffe AS, et al; Joint ESC/ACCF/AHA/WHF
Task Force for the Universal Denition of Myocardial Infarction. Third
universal denition of myocardial infarction. Eur Heart J 2012;33:
2551-67.
16. American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular
Angiography and Interventions. 2011 ACCF/AHA/SCAI Guideline for
Percutaneous Coronary Intervention. A report of the American College

26. Zhou L, Chen H. Prevention of contrast-induced nephropathy with

ascorbic acid. Intern Med 2012;51:531-5.
27. Jo SH, Koo BK, Park JS, et al. N-acetylcysteine versus AScorbic acid for
preventing contrast-Induced nephropathy in patients with renal insufciency undergoing coronary angiography NASPI studyda prospective
randomized controlled trial. Am Heart J 2009;157:576-83.
28. Boscheri A, Weinbrenner C, Botzek B, et al. Failure of ascorbic acid to
prevent contrast-media induced nephropathy in patients with renal
dysfunction. Clin Nephrol 2007;68:279-86.

Supplementary Material
To access the supplementary material accompanying this
article, visit the online version of the Canadian Journal of
Cardiology at www.onlinecjc.ca and at http://dx.doi.org/10.
1016/j.cjca.2013.08.018.